Gemcitabine

Identification

Summary

Gemcitabine is a nucleoside metabolic inhibitor used as adjunct therapy in the treatment of certain types of ovarian cancer, non-small cell lung carcinoma, metastatic breast cancer, and as a single agent for pancreatic cancer.

Brand Names
Gemzar, Infugem
Generic Name
Gemcitabine
DrugBank Accession Number
DB00441
Background

Gemcitabine is a nucleoside analog and a chemotherapeutic agent. It was originally investigated for its antiviral effects, but it is now used as an anticancer therapy for various cancers.1 Gemcitabine is a cytidine analog with two fluorine atoms replacing the hydroxyl on the ribose.3 As a prodrug, gemcitabine is transformed into its active metabolites that work by replacing the building blocks of nucleic acids during DNA elongation, arresting tumour growth and promoting apoptosis of malignant cells.6 The structure, metabolism, and mechanism of action of gemcitabine are similar to cytarabine, but gemcitabine has a wider spectrum of antitumour activity.2

Gemcitabine is marketed as Gemzar and it is available as intravenous injection. It is approved by the FDA to treat advanced ovarian cancer in combination with carboplatin, metastatic breast cancer in combination with paclitaxel, non-small cell lung cancer in combination with cisplatin, and pancreatic cancer as monotherapy.4 It is also being investigated in other cancer and tumour types.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 263.1981
Monoisotopic: 263.071762265
Chemical Formula
C9H11F2N3O4
Synonyms
  • 2'-Deoxy-2',2'-difluorocytidine
  • 2',2'-Difluorodeoxycytidine
  • 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one
  • Gemcitabin
  • Gemcitabina
  • Gemcitabine
  • Gemcitabinum
External IDs
  • LY-188011
  • LY188011

Pharmacology

Indication

Gemcitabine is a chemotherapeutic agent used as monotherapy or in combination with other anticancer agents.

In combination with carboplatin, it is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.4

Gemcitabine in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.4

In combination with cisplatin, gemcitabine is indicated for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC).4 Dual therapy with cisplatin is also used to treat patients with Stage IV (locally advanced or metastatic) transitional cell carcinoma (TCC) of the bladder.5

Gemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine is indicated for patients previously treated with fluorouracil.4

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary.4 Gemcitabine demonstrated cytotoxic effects against a broad range of cancer cell lines in vitro. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer.2 Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage.2 Gemcitabine inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months.3 In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months.2

Gemcitabine causes dose-limiting myelosuppression, such as anemia, leukopenia, neutropenia, and thrombocytopenia; however, events leading to discontinuation tend to occur less than 1% of the patients. Gemcitabine can elevate ALT, AST and alkaline phosphatase levels.3

Mechanism of action

Gemcitabine is a potent and specific deoxycytidine analog. After uptake into malignant cells, gemcitabine is phosphorylated by deoxycytidine kinase to form gemcitabine monophosphate, which is then converted to the active compounds, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These active metabolites are nucleosides that mediate antitumour effects. dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, thereby competitively inhibiting DNA chain elongation. The non-terminal position of dFdCTP in the DNA chain prevents detection of dFdCTP in the chain and repair by proof-reading 3′5′-exonuclease: this process is referred to as "masked DNA chain termination." Incorporation of dFdCTP into the DNA chain ultimately leads to chain termination, DNA fragmentation, and apoptotic cell death of malignant cells.2,3,4

Gemcitabine has self-potentiating pharmacological actions that can increase the probability of successful incorporation of gemcitabine triphosphate into the DNA chain: dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate dCTP for DNA synthesis. Since dFdCDP reduces the levels of dCTP, there is less competition for gemcitabine triphosphate for incorporation into DNA.2,4 Gemcitabine can also reduce metabolism and elimination of active metabolites from the target ce1l, prolonging high intracellular concentrations of the active metabolites. Such self-potentiating effects are not present with cytarabine.2

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Humans
UThymidylate synthase
inhibitor
Humans
UUMP-CMP kinase
inhibitor
Humans
Absorption

Peak plasma concentrations of gemcitabine range from 10 to 40 mg/L following a 30-minute intravenous infusion, and are reached at 15 to 30 minutes. One study showed that steady-state concentrations of gemcitabine showed a linear relationship to dose over the dose range 53 to 1000 mg/m2. Gemcitabine triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. In one study, the Cmax of gemcitabine triphosphate in peripheral blood mononuclear cells occurred within 30 minutes of the end of the infusion period and increased increased proportionally with gemcitabine doses of up to 350 mg/m2.2

Volume of distribution

In patients with various solid tumours, the volume of distribution increased with infusion length. The volume of distribution of gemcitabine was 50 L/m2 following infusions lasting less than 70 minutes. For long infusions, the volume of distribution rose to 370 L/m2.4

Gemcitabine triphosphate, the active metabolite of gemcitabine, accumulates and retains in solid tumour cells in vitro and in vivo. It is not extensively distributed to tissues after short infusions that last less than 70 minutes.2 It is not known whether gemcitabine crosses the blood-brain barrier, but gemcitabine is widely distributed into tissues, including ascitic fluid.6 In rats, placental and lacteal transfer occurred rapidly at five to 15 minutes following drug administration.1

Protein binding

Gemcitabine plasma protein binding is less than 10%.6

Metabolism

Following administration and uptake into cancer cells, gemcitabine is initially phosphorylated by deoxycytidine kinase (dCK), and to a lower extent, the extra-mitochondrial thymidine kinase 2 to form gemcitabine monophosphate (dFdCMP). dFdCMP is subsequently phosphorylated by nucleoside kinases to form active metabolites, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP).3 Gemcitabine is also deaminated intracellularly and extracellularly by cytidine deaminase to its inactive metabolite 2′,2′-difluorodeoxyuridine or 2´-deoxy-2´,2´-difluorouridine (dFdU). Deamination occurs in the blood, liver, kidneys, and other tissues,1 and this metabolic pathway accounts for most of drug clearance.3,6

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Route of elimination

Gemcitabine mainly undergoes renal excretion. Within a week following administration of a single dose of 1000 mg/m2 infused over 30 minutes, about 92-98% of the dose was recovered in urine where 89% of the recovered dose was excreted as difluorodeoxyuridine (dFdU) and less than 10% as gemcitabine.4 Monophosphate, diphosphate, or triphosphate metabolites of gemcitabine are not detectable in urine. In a single-dose study, about 1% of the administered dose was recovered in the feces.1

Half-life

Following intravenous infusions lasting less than 70 minutes, the terminal half-life ranged from 0.7 to 1.6 hours. Following infusions ranging from 70 to 285 minutes, the terminal half-life ranged from 4.1 to 10.6 hours.6 Females tend to have longer half-lives than male patients. Gemcitabine triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. The terminal half-life of gemcitabine triphosphate, the active metabolite, from mononuclear cells ranges from 1.7 to 19.4 hours.4

Clearance

Following intravenous infusions lasting less than 70 minutes, clearance ranged from 41 to 92 L/h/m2 in males and ranged from 31 to 69 L/h/m2 in females.6 Clearance decreases with age. Females have about 30% lower clearance than male patients.4

Adverse Effects
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Toxicity

The oral LD50 is 333 mg/kg in mice and >500 mg/kg in rats. The dermal LD50 in rabbits is >1000 mg/kg.7

There is no known antidote for gemcitabine overdose. In a dose-escalation study, patients were administered a single dose of gemcitabine as high as 5700 mg/m2 administered by intravenous infusion over 30 minutes every two weeks: main observed toxicities were myelosuppression, paresthesia, and severe rash. In the event of a suspected drug overdose, blood counts should be monitored, and patients should be provided with supportive therapy, as necessary.4

Pathways
PathwayCategory
Gemcitabine Metabolism PathwayDrug metabolism
Gemcitabine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Ribonucleoside-diphosphate reductase large subunit---(A;A)A allele, homozygous / A allele, homozygousADR Directly StudiedPatients with this genotype have increased risk of neutropenia and neurotoxicity with gemcitabine.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirGemcitabine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Gemcitabine.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Gemcitabine.
AceclofenacAceclofenac may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Gemcitabine.
AcetaminophenAcetaminophen may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Gemcitabine which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Gemcitabine.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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Product Ingredients
IngredientUNIICASInChI Key
Gemcitabine hydrochlorideU347PV74IL122111-03-9OKKDEIYWILRZIA-OSZBKLCCSA-N
International/Other Brands
Abine (Dosa) / Abingem (Miracalus) / Acytabin (Intas) / Celgem (Alkem) / Celzar (Celon) / Cytogem (Dr Reddys) / Daplax (Dr Reddys) / Dercin (Egis) / Eriogem (Eriochem) / Fotinex (Fada) / Gebina (Aspen) / Gembio (Bioprofarma) / Gemcired (Dr Reddys) / Gemita (Fresenius) / Gezt (Richmond) / Gitrabin (Actavis) / Gramagen (Lilly) / Jemta (Sandoz) / Nallian (Gedeon Richter) / Oncogem (Grey Inversiones) / Ribozar (Ribosepharm) / Tabin (Crinos) / Xtroz (Ranbaxy)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act GemcitabinePowder, for solution200 mg / vialIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act GemcitabinePowder, for solution1 g / vialIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act GemcitabineSolution38 mg / mLIntravenousActavis Pharma Company2016-05-022019-08-13Canada flag
GemcitabineInjection, solution38 mg/1mLIntravenousHospira, Inc.2011-08-26Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousBluePoint Laboratories2018-05-25Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousBluePoint Laboratories2018-05-25Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousAccord Healthcare Inc.2018-01-24Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousHospira, Inc.2011-08-24Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousBluePoint Laboratories2018-05-25Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousMylan Laboratories Limited2017-12-31Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aj-gemcitabinePowder, for solution200 mg / vialIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
Aj-gemcitabinePowder, for solution2 g / vialIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
Aj-gemcitabinePowder, for solution1 g / vialIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
GemcitabineInjection, solution200 mg/5.26mLIntravenousMylan Institutional LLC2018-01-03Not applicableUS flag
GemcitabineInjection, powder, lyophilized, for solution2 g/50mLIntravenousFresenius Kabi USA, LLC2011-05-17Not applicableUS flag
GemcitabineInjection, powder, lyophilized, for solution38 mg/1mLIntravenousHospira, Inc.2011-07-26Not applicableUS flag
GemcitabineInjection, powder, lyophilized, for solution1 g/1IntravenousShilpa Medicare Limited2018-06-06Not applicableUS flag
GemcitabineInjection, powder, lyophilized, for solution1 g/25mLIntravenousSagent Pharmaceuticals2011-07-252017-07-31US flag
GemcitabineInjection, solution38 mg/1mLIntravenousApotex Corp.2018-03-202021-01-31US flag
GemcitabineInjection, powder, lyophilized, for solution1 g/1IntravenousMeitheal Pharmaceuticals Inc.2018-11-01Not applicableUS flag

Categories

ATC Codes
L01BC05 — Gemcitabine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Pyrimidones / Aminopyrimidines and derivatives / Hydropyrimidines / Imidolactams / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Fluorohydrins / Azacyclic compounds / Oxacyclic compounds
show 7 more
Substituents
Alcohol / Alkyl fluoride / Alkyl halide / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Fluorohydrin / Halohydrin / Heteroaromatic compound
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, pyrimidine 2'-deoxyribonucleoside (CHEBI:175901)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
B76N6SBZ8R
CAS number
95058-81-4
InChI Key
SDUQYLNIPVEERB-QPPQHZFASA-N
InChI
InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
IUPAC Name
4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F

References

Synthesis Reference

John A. Weigel, "Process for making gemcitabine hydrochloride." U.S. Patent US6001994, issued May, 1995.

US6001994
General References
  1. Noble S, Goa KL: Gemcitabine. A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer. Drugs. 1997 Sep;54(3):447-72. doi: 10.2165/00003495-199754030-00009. [Article]
  2. Toschi L, Finocchiaro G, Bartolini S, Gioia V, Cappuzzo F: Role of gemcitabine in cancer therapy. Future Oncol. 2005 Feb;1(1):7-17. doi: 10.1517/14796694.1.1.7. [Article]
  3. Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E: Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016 Jul;78(1):1-12. doi: 10.1007/s00280-016-3003-0. Epub 2016 Mar 23. [Article]
  4. FDA Approved Drug Products: GEMZAR (gemcitabine) for injection, for intravenous use [Link]
  5. Product Monograph: GEMCITABINE Intravenous Injection [Link]
  6. BC Cancer: Gemcitabine Monograph [Link]
  7. Pfizer: Gemcitabine Safety Data Sheet [Link]
Human Metabolome Database
HMDB0014584
KEGG Drug
D02368
KEGG Compound
C07650
PubChem Compound
60750
PubChem Substance
46506425
ChemSpider
54753
BindingDB
429521
RxNav
12574
ChEBI
175901
ChEMBL
CHEMBL888
ZINC
ZINC000018279854
Therapeutic Targets Database
DAP001246
PharmGKB
PA449748
PDBe Ligand
GEO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gemcitabine
PDB Entries
1p62 / 2no0 / 2vpp / 4pd5 / 6nl4
FDA label
Download (105 KB)
MSDS
Download (69.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentNon Small Cell Lung Cancer Squamous (NSCLC-Sq)1
4CompletedTreatmentAdenocarcinomas of the Pancreas1
4CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
4Not Yet RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
4RecruitingTreatmentHemophagocytic Syndrome (HPS) / T/NK-Cell Lymphoma1
4RecruitingTreatmentPancreatic Adenocarcinoma (Ductal Adenocarcinoma)1
4RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL)2
4TerminatedTreatmentEGFR Activating Mutation / Metastatic Non-Small Cell Lung Cancer1
4TerminatedTreatmentMalignant Neoplasm of Pancreas1
4TerminatedTreatmentRenal Cell Adenocarcinoma1

Pharmacoeconomics

Manufacturers
  • Teva parenteral medicines inc
  • Eli lilly and co
Packagers
  • Eli Lilly & Co.
Dosage Forms
FormRouteStrength
SolutionIntravenous38 mg / mL
InjectionIntravenous1 G
Powder, for solution
Injection, solution, concentrateIntravenous; Parenteral40 MG/ML
SolutionIntravenous1 g
Injection, solution, concentrateIntravenous
Injection, powder, for solutionParenteral
SolutionIntravenous10 mg
Solution, concentrateIntravenous10 mg
Injection, powder, lyophilized, for solutionIntravenous1 g
Injection, powder, lyophilized, for solutionIntravenous200 mg
SolutionIntravenous40 mg
Injection, solution, concentrateIntravenous; Parenteral100 MG/ML
Powder, for solutionIntravenous38 MG/ML
Powder, for solutionParenteral38 MG/ML
Powder, for solutionParenteral1 G
Powder, for solutionParenteral2 G
Powder, for solutionParenteral200 MG
Injection, solution, concentrateIntravenous; Parenteral38 MG/ML
Injection, solutionParenteral10 MG/ML
InjectionIntravenous1 g/26.3mL
InjectionIntravenous2 g/52.6mL
InjectionIntravenous200 mg/5.26mL
InjectionIntravenous38 mg/1mL
Injection, powder, for solutionIntravenous200 MG
Injection, powder, lyophilized, for solutionIntravenous1 g/1
Injection, powder, lyophilized, for solutionIntravenous200 mg/1
Injection, powder, lyophilized, for solutionIntravenous40 mg/1mL
Injection, solutionIntravenous1 g/26.3mL
Injection, solutionIntravenous100 mg/1mL
Injection, solutionIntravenous2 g/52.6mL
Injection, solutionIntravenous200 mg/5.26mL
Injection, solutionIntravenous38 mg/1mL
InjectionIntravenous
Powder, for solutionIntravenous1 g / vial
Powder, for solutionIntravenous200 mg / vial
SolutionIntravenous100 mg / mL
Injection, powder, for solution1000 mg/1vial
PowderIntravenous1 g / vial
PowderIntravenous2 g / vial
PowderIntravenous200 mg / vial
Powder, for solutionIntravenous2 g / vial
Injection, powder, lyophilized, for solutionIntravenous1 g/25mL
Injection, powder, lyophilized, for solutionIntravenous200 mg/5mL
SolutionIntravenous
Injection, powder, lyophilized, for solutionIntravenous2 g/50mL
Injection, powder, lyophilized, for solutionIntravenous38 mg/1mL
SolutionIntravenous40 mg / mL
Injection, powder, for solutionIntravenous
PowderIntravenous1000 mg/1vial
PowderIntravenous200 mg/1vial
Injection, powder, lyophilized, for solutionIntravenous200 mg/1vial
Injection, solutionIntravenous
Injection, powder, lyophilized, for solutionIntravenous
Injection, powder, for solution200 mg/1vial
Injection, solution, concentrateParenteral
Injection, powder, for solutionIntravenous1 g
Cream
Injection, powder, for solution
Injection, solutionIntravenous10 mg/1mL
Injection, solution, concentrateIntravenous38 MG/ML
Solution, concentrateIntravenous38 mg
Injection, powder, lyophilized, for solutionIntravenous1000 mg
PowderIntravenous1400 mg/1vial
Injection, powder, lyophilized, for solutionIntravenous1000 mg/1vial
Prices
Unit descriptionCostUnit
Gemzar 1 gm Solution Vial903.93USD vial
Gemzar 1 gram vial869.16USD vial
Gemzar 200 mg Solution Vial180.78USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5464826No1995-11-072013-05-07US flag
US4808614No1989-02-282010-05-15US flag
US9241948No2016-01-262033-07-01US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility15.3 g/Lhttps://cdn.pfizer.com/pfizercom/products/material_safety_data/Gemcitabine_Injection_(Hospira)16-Nov-2016.pdf
logP-1.4Not Available
pKa3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility22.3 mg/mLALOGPS
logP0.14ALOGPS
logP-1.5ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)11.52ChemAxon
pKa (Strongest Basic)3.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area108.38 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity53.25 m3·mol-1ChemAxon
Polarizability21.62 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9814
Blood Brain Barrier+0.9693
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.8317
P-glycoprotein inhibitor INon-inhibitor0.9557
P-glycoprotein inhibitor IINon-inhibitor0.9106
Renal organic cation transporterNon-inhibitor0.939
CYP450 2C9 substrateNon-substrate0.8634
CYP450 2D6 substrateNon-substrate0.8484
CYP450 3A4 substrateNon-substrate0.6016
CYP450 1A2 substrateNon-inhibitor0.8958
CYP450 2C9 inhibitorNon-inhibitor0.8633
CYP450 2D6 inhibitorNon-inhibitor0.8787
CYP450 2C19 inhibitorNon-inhibitor0.8478
CYP450 3A4 inhibitorNon-inhibitor0.9032
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8862
Ames testNon AMES toxic0.6793
CarcinogenicityNon-carcinogens0.8286
BiodegradationNot ready biodegradable0.9948
Rat acute toxicity2.1220 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9948
hERG inhibition (predictor II)Non-inhibitor0.8314
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0930000000-e2122f1423d3060097b9
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0790000000-e66897c78fa010a45ab8
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0cfs-0910000000-e4e73c07b687772a1108
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-99f619802e3ba7bd8b2e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-18dd55d7372a11b9dfb7
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-1900000000-fdc016f6d17808e4cf1b
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-5900000000-ec478d4dfe03f80b91ad
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0790000000-0d953fc9632751f00f72
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-07xs-0920000000-0e8154089a57b6bef7c4
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-c54a530153a028d6ffcc
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-1f4cd6bc7d377fe7731e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-c3cdcfa5d386ac7222fa
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0aor-4900000000-337f45a27b7b12b1b2f0
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0920000000-52d24e07b71b7d08dcdb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0190000000-6d052797bc5b8b31bf7b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03dl-0900000000-01d92fca070f980c2668
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-95712722811cd50ab160
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0190000000-b97d64dba479bbac0253
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0930000000-fce77aa139fbedd4910b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-179a77c420afc3af2544
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-1900000000-5569d5d510ca5c1a84ef
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-2900000000-eb92e15ff6bb6fafe1dd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-5900000000-7cec5b636c875dcbfced
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0190000000-8d1e58453b0a991c8106
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0930000000-4739133fc80b45fc52ba
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-8fc0422b65b946f62385
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-1900000000-da3f8b2e4b3babb2a4f0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-2900000000-ea359abde4b5c6deb936
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-5900000000-f8e5e85ba0cd765dff4c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-18896272b82c17bec731

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Cross-linking/alkylation
Curator comments
Incorporation into DNA is mediated by the active metabolite, gemcitabine triphosphate.
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Hastak K, Alli E, Ford JM: Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010 Oct 15;70(20):7970-80. doi: 10.1158/0008-5472.CAN-09-4521. Epub 2010 Aug 26. [Article]
  2. Ledermann JA, Gabra H, Jayson GC, Spanswick VJ, Rustin GJ, Jitlal M, James LE, Hartley JA: Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin Cancer Res. 2010 Oct 1;16(19):4899-905. doi: 10.1158/1078-0432.CCR-10-0832. Epub 2010 Aug 18. [Article]
  3. Garcia-Diaz M, Murray MS, Kunkel TA, Chou KM: Interaction between DNA Polymerase lambda and anticancer nucleoside analogs. J Biol Chem. 2010 May 28;285(22):16874-9. doi: 10.1074/jbc.M109.094391. Epub 2010 Mar 26. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
This enzyme is inhibited by the active metabolite of gemcitabine, gemcitabine diphosphate.
General Function
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name
RRM1
Uniprot ID
P23921
Uniprot Name
Ribonucleoside-diphosphate reductase large subunit
Molecular Weight
90069.375 Da
References
  1. Kwon WS, Rha SY, Choi YH, Lee JO, Park KH, Jung JJ, Kim TS, Jeung HC, Chung HC: Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics. 2006 Jun;16(6):429-38. [Article]
  2. Rosell R, Cobo M, Isla D, Camps C, Massuti B: Pharmacogenomics and gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v13-16. [Article]
  3. Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G: RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006 Oct 10;24(29):4731-7. Epub 2006 Sep 11. [Article]
  4. Smid K, Bergman AM, Eijk PP, Veerman G, van Haperen VW, van den Ijssel P, Ylstra B, Peters GJ: Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1001-7. [Article]
  5. Nakahira S, Nakamori S, Tsujie M, Takahashi Y, Okami J, Yoshioka S, Yamasaki M, Marubashi S, Takemasa I, Miyamoto A, Takeda Y, Nagano H, Dono K, Umeshita K, Sakon M, Monden M: Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer. 2007 Mar 15;120(6):1355-63. [Article]
  6. Cerqueira NM, Fernandes PA, Ramos MJ: Understanding ribonucleotide reductase inactivation by gemcitabine. Chemistry. 2007;13(30):8507-15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Thymidylate synthase activity
Specific Function
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name
TYMS
Uniprot ID
P04818
Uniprot Name
Thymidylate synthase
Molecular Weight
35715.65 Da
References
  1. Rosell R, Taron M, Sanchez JM, Moran T, Reguart N, Besse B, Isla D, Massuti B, Alberola V, Sanchez JJ: The promise of pharmacogenomics: gemcitabine and pemetrexed. Oncology (Williston Park). 2004 Nov;18(13 Suppl 8):70-6. [Article]
  2. Huang CL, Yokomise H, Fukushima M, Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2006 Apr;2(2):289-99. [Article]
  3. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [Article]
  4. Zhao XD, Zhang Y: [Routine chemotherapeutic drug treatment effectiveness predictive molecules and chemotherapeutic drug selection]. Ai Zheng. 2006 Dec;25(12):1577-80. [Article]
  5. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Del Tacca M, Danesi R: Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol Cancer Ther. 2006 Jun;5(6):1387-95. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Uridylate kinase activity
Specific Function
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as...
Gene Name
CMPK1
Uniprot ID
P30085
Uniprot Name
UMP-CMP kinase
Molecular Weight
22222.175 Da
References
  1. Vernejoul F, Ghenassia L, Souque A, Lulka H, Drocourt D, Cordelier P, Pradayrol L, Pyronnet S, Buscail L, Tiraby G: Gene therapy based on gemcitabine chemosensitization suppresses pancreatic tumor growth. Mol Ther. 2006 Dec;14(6):758-67. Epub 2006 Sep 25. [Article]
  2. Hsu CH, Liou JY, Dutschman GE, Cheng YC: Phosphorylation of Cytidine, Deoxycytidine, and Their Analog Monophosphates by Human UMP/CMP Kinase Is Differentially Regulated by ATP and Magnesium. Mol Pharmacol. 2005 Mar;67(3):806-14. Epub 2004 Nov 18. [Article]
  3. Maring JG, Groen HJ, Wachters FM, Uges DR, de Vries EG: Genetic factors influencing pyrimidine-antagonist chemotherapy. Pharmacogenomics J. 2005;5(4):226-43. [Article]
  4. Lam W, Leung CH, Bussom S, Cheng YC: The impact of hypoxic treatment on the expression of phosphoglycerate kinase and the cytotoxicity of troxacitabine and gemcitabine. Mol Pharmacol. 2007 Sep;72(3):536-44. Epub 2007 Jun 12. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Gene Name
CDA
Uniprot ID
P32320
Uniprot Name
Cytidine deaminase
Molecular Weight
16184.545 Da
References
  1. Giovannetti E, Laan AC, Vasile E, Tibaldi C, Nannizzi S, Ricciardi S, Falcone A, Danesi R, Peters GJ: Correlation between cytidine deaminase genotype and gemcitabine deamination in blood samples. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):720-5. doi: 10.1080/15257770802145447. [Article]
  2. Gusella M, Pasini F, Bolzonella C, Meneghetti S, Barile C, Bononi A, Toso S, Menon D, Crepaldi G, Modena Y, Stievano L, Padrini R: Equilibrative nucleoside transporter 1 genotype, cytidine deaminase activity and age predict gemcitabine plasma clearance in patients with solid tumours. Br J Clin Pharmacol. 2011 Mar;71(3):437-44. doi: 10.1111/j.1365-2125.2010.03838.x. [Article]
  3. Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
Molecular Weight
30518.315 Da
References
  1. Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [Article]
  2. Marechal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Salmon I, Deviere J, Van Laethem JL: Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma. Cancer. 2010 Nov 15;116(22):5200-6. doi: 10.1002/cncr.25303. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Thymidine kinase activity
Specific Function
Deoxyribonucleoside kinase that phosphorylates thymidine, deoxycytidine, and deoxyuridine. Also phosphorylates anti-viral and anti-cancer nucleoside analogs.
Gene Name
TK2
Uniprot ID
O00142
Uniprot Name
Thymidine kinase 2, mitochondrial
Molecular Weight
31004.53 Da
References
  1. Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E: Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016 Jul;78(1):1-12. doi: 10.1007/s00280-016-3003-0. Epub 2016 Mar 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Uridylate kinase activity
Specific Function
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as...
Gene Name
CMPK1
Uniprot ID
P30085
Uniprot Name
UMP-CMP kinase
Molecular Weight
22222.175 Da
References
  1. Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E: Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016 Jul;78(1):1-12. doi: 10.1007/s00280-016-3003-0. Epub 2016 Mar 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Ribosomal small subunit binding
Specific Function
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-sit...
Gene Name
NME1
Uniprot ID
P15531
Uniprot Name
Nucleoside diphosphate kinase A
Molecular Weight
17148.635 Da
References
  1. Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E: Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016 Jul;78(1):1-12. doi: 10.1007/s00280-016-3003-0. Epub 2016 Mar 23. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Bergman AM, Pinedo HM, Talianidis I, Veerman G, Loves WJ, van der Wilt CL, Peters GJ: Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. Br J Cancer. 2003 Jun 16;88(12):1963-70. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Santini D, Vincenzi B, Fratto ME, Perrone G, Lai R, Catalano V, Cass C, Ruffini PA, Spoto C, Muretto P, Rizzo S, Muda AO, Mackey JR, Russo A, Tonini G, Graziano F: Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer. J Cell Physiol. 2010 May;223(2):384-8. doi: 10.1002/jcp.22045. [Article]
  2. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [Article]
  3. Wang H, Word BR, Lyn-Cook BD: Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrative nucleoside transporter 1. Anticancer Res. 2011 Oct;31(10):3171-80. [Article]
  4. Morinaga S, Nakamura Y, Watanabe T, Mikayama H, Tamagawa H, Yamamoto N, Shiozawa M, Akaike M, Ohkawa S, Kameda Y, Miyagi Y: Immunohistochemical analysis of human equilibrative nucleoside transporter-1 (hENT1) predicts survival in resected pancreatic cancer patients treated with adjuvant gemcitabine monotherapy. Ann Surg Oncol. 2012 Jul;19 Suppl 3:S558-64. doi: 10.1245/s10434-011-2054-z. Epub 2011 Sep 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine)....
Gene Name
SLC28A1
Uniprot ID
O00337
Uniprot Name
Sodium/nucleoside cotransporter 1
Molecular Weight
71583.18 Da
References
  1. Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
Gene Name
SLC29A2
Uniprot ID
Q14542
Uniprot Name
Equilibrative nucleoside transporter 2
Molecular Weight
50112.335 Da
References
  1. Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtyp...
Gene Name
SLC28A3
Uniprot ID
Q9HAS3
Uniprot Name
Solute carrier family 28 member 3
Molecular Weight
76929.61 Da
References
  1. Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD: Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22. [Article]

Drug created on June 13, 2005 13:24 / Updated on September 28, 2021 07:54